What is the mechanism of action of hydroxyzine (an antihistamine) in the treatment of interstitial cystitis?

From the Guidelines

Hydroxyzine is effective for treating interstitial cystitis (IC) because it blocks histamine receptors, which helps reduce inflammation and pain in the bladder. The medication works by inhibiting mast cell degranulation in the bladder wall, reducing the release of inflammatory mediators that contribute to IC symptoms 1. This antihistamine effect also helps with sleep and anxiety, which are often problematic for IC patients.

Key Points

• Hydroxyzine is typically prescribed at 10-25 mg at bedtime initially, which may be increased to 25-75 mg daily in divided doses if needed.
• Treatment duration is usually several weeks to months, with some patients requiring long-term therapy.
• Side effects may include drowsiness, dry mouth, and constipation, so it's best taken at bedtime initially.
• Hydroxyzine is particularly helpful for patients whose IC symptoms worsen with allergic flares or stress.
• It may take 2-3 weeks to notice improvement, and the medication should not be stopped abruptly after long-term use.
• For optimal results, hydroxyzine is often combined with other IC treatments like dietary modifications, pelvic floor therapy, or other medications, as recommended by the American Urological Association Education and Research, Inc. 1. The AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome provides a comprehensive approach to managing IC, including the use of hydroxyzine as a treatment option 1.

From the FDA Drug Label

Hydroxyzine hydrochloride is unrelated chemically to the phenothiazines, reserpine, meprobamate or the benzodiazepines. Hydroxyzine is not a cortical depressant, but its action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system. The mechanism of action of hydroxyzine in the treatment of interstitial cystitis is not explicitly stated in the provided drug label.

• The label mentions various effects of hydroxyzine, including antihistaminic, analgesic, and antiemetic effects, as well as skeletal muscle relaxation and bronchodilator activity.
• However, it does not provide information on how these effects relate to the treatment of interstitial cystitis. 2

From the Research

Mechanism of Action of Hydroxyzine

The mechanism of action of hydroxyzine in the treatment of interstitial cystitis is not fully understood, but several studies provide some insights:

• Hydroxyzine is a piperazine, tricyclic, H1-receptor antagonist with unique properties, especially the inhibition of mast cell and neuronal secretion 3.
• The inhibition of mast cell activation is thought to be an important component of the treatment of interstitial cystitis, as mast cell activation is believed to play a role in the pathogenesis of the disease 4, 5, 6.
• Hydroxyzine may also have an effect on neurogenic inflammation, which is another proposed mechanism of interstitial cystitis 4, 5, 6.
• The exact mechanism of action of hydroxyzine in reducing interstitial cystitis symptoms is not fully understood, but preliminary results indicate that it has an unusual ability to reduce symptoms 3.

Treatment Approaches

Hydroxyzine is often used as part of a multimodal treatment approach for interstitial cystitis, which may include:

• Oral therapies such as amitriptyline, cyclosporine A, and pentosan polysulfate sodium (PPS) 5, 6, 7.
• Intravesical instillation therapy using lidocaine, heparin, or PPS 5, 6.
• Behavioral interventions and patient education 5, 6.